rs1877724

chr1-225825654-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136018.4(EPHX1):c.-5-3071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,190 control chromosomes in the GnomAD database, including 4,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4155 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

Genes affected

EPHX1 (HGNC:3401): (epoxide hydrolase 1) Epoxide hydrolase is a critical biotransformation enzyme that converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body. Epoxide hydrolase functions in both the activation and detoxification of epoxides. Mutations in this gene cause preeclampsia, epoxide hydrolase deficiency or increased epoxide hydrolase activity. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.-5-3071C>T		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.-5-3071C>T		intron_variant		1	NM_001136018.4	P1
EPHX1	ENST00000366837.5	c.-6+110C>T		intron_variant		1		P1
EPHX1	ENST00000614058.4	c.-5-3071C>T		intron_variant		1		P1
EPHX1	ENST00000448202.5	c.-5-3071C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32618 AN: 152046 Hom.: 4155 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.192 AC: 5 AN: 26 Hom.: 1 AF XY: 0.167 AC XY: 4 AN XY: 24

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.214 AC: 32612 AN: 152164 Hom.: 4155 Cov.: 32 AF XY: 0.216 AC XY: 16078 AN XY: 74392

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.207

Alfa AF: 0.258 Hom.: 7530

Bravo AF: 0.207

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.8
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1877724; hg19: chr1-226013355;